Palladium-Catalyzed Annulations of an Anti-Bredt Olefin

A famous class of alkene-containing compounds that have intrigued chemists for more than a century are anti-Bredt olefins (ABOs). ABOs are a subclass of bridgehead alkenes that reside in small ring systems, thus rendering them unstable and historically challenging to leverage in chemical synthesis. The present study describes metal catalyzed reactions of a [2.2.1]-bridged bicyclic ABO, wherein two in situ-generated species, both present in low concentration and generated transiently, undergo a productive reaction. The transformation uses palladium catalysis to unite the aforementioned ABO with indole-based trapping partners, thus delivering unusual heterocyclic products. The scope of the reaction is reported, as well as computations concerning the putative Pd-bound ABO species. The latter suggests that the short-lived ABO is stabilized by Pd via the energetically favorable formation of an intermediate palladacycle. This methodology is expected to prompt the further development of unconventional reactions, including metal-catalyzed processes of ABOs and other transient olefins.